mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation.

Messenger RNA (mRNA) vaccines have revolutionized the field of vaccinology, offering rapid design flexibility, scalable manufacturing, and strong immunogenicity. The unprecedented success of COVID-19 mRNA vaccines has accelerated research into novel delivery platforms and expanded therapeutic applications beyond infectious diseases to cancer immunotherapy and immune-mediated disorders. This review provides a comprehensive overview of the mechanistic principles underlying mRNA vaccine design, including mRNA engineering strategies, delivery innovations such as lipid nanoparticles (LNPs), polymeric nanoparticles (PNPs), and virus-like particles (VLPs), as well as emerging needle-free administration technologies. We further highlight recent advances in therapeutic areas spanning infectious diseases (e.g. HIV, tuberculosis, respiratory syncytial virus), oncology, and non-traditional indications such as autoimmune disorders. Despite remarkable progress, critical challenges persist in vaccine stability, delivery efficiency, large-scale manufacturing, and global accessibility. Finally, we discuss future research directions integrating artificial intelligence, nanotechnology, and systems immunology to accelerate next-generation mRNA vaccine development and clinical translation.